Jonas S, Springmeier G, Tauber R, Wiedenmann B, Gessner R, Kling N, Lobeck H, Fieger C, Bechstein W O, Neuhaus P
Department of Surgery, Virchow Klinikum, Humboldt Universität, Augustenburger Platz 1, D-13353 Berlin, Germany.
World J Surg. 1997 Sep;21(7):768-72. doi: 10.1007/s002689900303.
In gallbladder carcinoma, studies on the prime target of genetic alterations and gene therapy in human gallbladder malignancies, the p53 tumor suppressor gene, have been focusing on this gene's immunohistochemical detection. From November 1991 to October 1993, seven patients suffering from gallbladder carcinoma underwent surgical resection. Cancerous and normal liver tissues were obtained immediately after surgery, snap-frozen in liquid nitrogen, and stored at -80 degrees C for immunohistochemistry and DNA isolation. Exons 5, 6, 7, and 8 of the p53 gene were completely sequenced following polymerase chain reaction (PCR) amplification of a 1574-bp fragment. Missense mutations were detected in the cancerous tissues of two patients: one transition each on codons 134 (Phe-->Leu) and 146 (Trp-->Arg). Immunohistochemical p53 staining was positive in the latter patient only. This is the first report on sequence analysis and mutagenesis of the p53 gene in Caucasian patients with gallbladder cancer. Both mutations were transitions and seem to represent a rather rare event. The possible impact of p53 mutagenesis on gallbladder tumorigenesis requires evaluation in larger studies.
在胆囊癌中，针对人类胆囊恶性肿瘤中基因改变的主要靶点和基因治疗的研究，即p53肿瘤抑制基因，一直聚焦于该基因的免疫组织化学检测。1991年11月至1993年10月，7例胆囊癌患者接受了手术切除。术后立即获取癌组织和正常肝组织，在液氮中速冻，并储存在-80℃用于免疫组织化学和DNA提取。在对一个1574碱基对片段进行聚合酶链反应（PCR）扩增后，对p53基因的外显子5、6、7和8进行了全序列测定。在两名患者的癌组织中检测到错义突变：分别在密码子134（苯丙氨酸→亮氨酸）和146（色氨酸→精氨酸）处各有一个转换。仅在后一名患者中免疫组织化学p53染色呈阳性。这是关于白种人胆囊癌患者p53基因序列分析和诱变的首次报告。两种突变均为转换，似乎是相当罕见的事件。p53诱变对胆囊肿瘤发生的可能影响需要在更大规模的研究中进行评估。
